PMID- 36720002 OWN - NLM STAT- MEDLINE DCOM- 20230421 LR - 20230616 IS - 1097-4547 (Electronic) IS - 0360-4012 (Linking) VI - 101 IP - 6 DP - 2023 Jun TI - Intrahippocampal injection of IL-1beta upregulates Siah1-mediated degradation of synaptophysin by activation of the ERK signaling in male rat. PG - 930-951 LID - 10.1002/jnr.25170 [doi] AB - Interleukin-1beta (IL-1beta) has been described to exert important effect on synapses in the brain. Here, we explored if the synapses in the hippocampus would be adversely affected following intracerebral IL-1beta injection and, if so, to clarify the underlying molecular mechanisms. Adult male Sprague-Dawley rats were divided into control, IL-1beta, IL-1beta + PD98059, and IL-1beta + MG132 groups and then sacrificed for detection of synaptophysin (syn) protein level, synaptosome glutamate release, and synapse ultrastructure by western blotting, glutamate kit and electron microscopy, respectively. These rats were tested by Morris water maze for learning and memory ability. It was determined by western blotting whether IL-1beta exerted the effect of on syn and siah1 expression in primary neurons via extracellular regulated protein kinases (ERK) signaling pathway. Intrahippocampal injection of IL-1beta in male rats and sacrificed at 8d resulted in a significant decrease in syn protein, damage of synapse structure, and abnormal release of neurotransmitters glutamate. ERK inhibitor and proteosome inhibitor treatment reversed the above changes induced by IL-1beta both in vivo and in vitro. In primary cultured neurons incubated with IL-1beta, the expression level of synaptophysin was significantly downregulated coupled with abnormal glutamate release. Furthermore, use of PD98059 had confirmed that ERK signaling pathway was implicated in synaptic disorders caused by IL-1beta treatment. The present results suggest that exogenous IL-1beta can suppress syn protein level and glutamate release. A possible mechanism for this is that IL-1beta induces syn degradation that is regulated by the E3 ligase siah1 via the ERK signaling pathway. CI - (c) 2023 Wiley Periodicals LLC. FAU - Zhou, Qiuping AU - Zhou Q AD - School of Medicine, South China University of Technology, Guangzhou, China. AD - Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. FAU - Lin, Lanfen AU - Lin L AD - Guangdong Second Provincial General Hospital, Guangzhou, China. FAU - Li, Haiyan AU - Li H AD - Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. FAU - Li, Yichen AU - Li Y AD - Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. FAU - Liu, Nan AU - Liu N AD - School of Medicine, South China University of Technology, Guangzhou, China. AD - Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. FAU - Wang, Huifang AU - Wang H AD - Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. FAU - Jiang, Shuqi AU - Jiang S AD - Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. FAU - Li, Qian AU - Li Q AD - Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. AD - Southern Medical University, Guangzhou, China. FAU - Chen, Zhuo AU - Chen Z AD - School of Medicine, South China University of Technology, Guangzhou, China. AD - Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. FAU - Lin, Yiyan AU - Lin Y AD - Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. AD - Southern Medical University, Guangzhou, China. FAU - Jin, Hui AU - Jin H AD - Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. FAU - Deng, Yiyu AU - Deng Y AUID- ORCID: 0000-0002-0459-7399 AD - School of Medicine, South China University of Technology, Guangzhou, China. AD - Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230131 PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Glutamates) RN - 0 (Interleukin-1beta) RN - EC 2.7.- (Protein Kinases) RN - 0 (Synaptophysin) RN - EC 2.3.2.27 (seven in absentia proteins) SB - IM MH - Animals MH - Male MH - Rats MH - Glutamates MH - Interleukin-1beta/metabolism MH - *Protein Kinases/metabolism MH - Rats, Sprague-Dawley MH - *Signal Transduction MH - Synaptophysin/metabolism OTO - NOTNLM OT - ERK OT - IL-1beta OT - RRID:AB_10679361 OT - RRID:AB_10687612 OT - RRID:AB_2107436 OT - RRID:AB_2124750 OT - RRID:AB_2198854 OT - RRID:AB_2270373 OT - RRID:AB_2888314 OT - RRID:AB_2904530 OT - RRID:AB_303248 OT - RRID:AB_561049 OT - RRID:AB_671515 OT - RRID:RGD_70508 OT - RRID:SCR_002798 OT - RRID:SCR_003070 OT - glutamate OT - neuroinflammation OT - siah1 OT - synaptophysin EDAT- 2023/02/01 06:00 MHDA- 2023/04/20 06:41 CRDT- 2023/01/31 14:53 PHST- 2022/12/21 00:00 [revised] PHST- 2022/05/21 00:00 [received] PHST- 2023/01/13 00:00 [accepted] PHST- 2023/04/20 06:41 [medline] PHST- 2023/02/01 06:00 [pubmed] PHST- 2023/01/31 14:53 [entrez] AID - 10.1002/jnr.25170 [doi] PST - ppublish SO - J Neurosci Res. 2023 Jun;101(6):930-951. doi: 10.1002/jnr.25170. Epub 2023 Jan 31.